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CD138 multiple myeloma

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https://www.readbyqxmd.com/read/27924158/lycorine-downregulates-hmgb1-to-inhibit-autophagy-and-enhances-bortezomib-activity-in-multiple-myeloma
#1
Mridul Roy, Long Liang, Xiaojuan Xiao, Yuanliang Peng, Yuhao Luo, Weihua Zhou, Ji Zhang, Lugui Qiu, Shuaishuai Zhang, Feng Liu, Mao Ye, Wen Zhou, Jing Liu
Multiple myeloma (MM) is largely incurable and drug-resistant. Novel therapeutic approaches such as inhibiting autophagy or rational drug combinations are aimed to overcome this issue. In this study, we found that lycorine exhibits a promising anti-proliferative activity against MM in vitro and in vivo by inhibiting autophagy. We identified High mobility group box 1 (HMGB1), an important regulator of autophagy, as the most aberrantly expressed protein after lycorine treatment and as a critical mediator of lycorine activity...
2016: Theranostics
https://www.readbyqxmd.com/read/27903712/the-myeloma-stem-cell-concept-revisited-from-phenomenology-to-operational-terms
#2
REVIEW
Hans Erik Johnsen, Martin Bøgsted, Alexander Schmitz, Julie Støve Bødker, Tarec Christoffer El-Galaly, Preben Johansen, Peter Valent, Niklas Zojer, Els Van Valckenborgh, Karin Vanderkerken, Mark van Duin, Pieter Sonneveld, Martin Perez-Andres, Alberto Orfao, Karen Dybkær
The concept of the myeloma stem cell may have important therapeutic implications, yet its demonstration has been hampered by a lack of consistency in terms and definitions. Here, we summarize the current documentation and propose single-cell in vitro studies for future translational studies. By the classical approach, a CD19(-)/CD45(low/-)/CD38(high)/CD138(+) malignant plasma cell, but not the CD19(+)/CD38(low/-) memory B cell compartment, is enriched for tumorigenic cells that initiate myeloma in xenografted immunodeficient mice, supporting that myeloma stem cells are present in the malignant PC compartment...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#3
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27902770/mitochondrial-targeted-decyl-triphenylphosphonium-enhances-2-deoxy-d-glucose-mediated-oxidative-stress-and-clonogenic-killing-of-multiple-myeloma-cells
#4
Jeanine Schibler, Ann M Tomanek-Chalkley, Jessica L Reedy, Fenghuang Zhan, Douglas R Spitz, Michael K Schultz, Apollina Goel
Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog...
2016: PloS One
https://www.readbyqxmd.com/read/27868410/-expression-of-microrna-221-222-in-patients-with-monoclonal-gammopathy-of-undetermined-significance-and-multiple-myeloma
#5
Suwen Yang, Wei Wang, Hong Jin, Yuhong Zhong, Xinyou Xie
Objective: To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM. Methods: Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27861307/epibulbar-plasmacytoma-masquerading-as-subconjunctival-hemorrhage-in-a-patient-with-multiple-myeloma
#6
Amanda Bradley, Amy Estes, Lane Ulrich, Dilip Thomas, David Gay
PURPOSE: We report a 75-year-old woman with a history of multiple myeloma immunoglobulin D (IgD) variant, who presented with an epibulbar plasmacytoma masquerading as a subconjunctival hemorrhage. METHODS: Magnetic resonance imaging of the brain and orbits with and without contrast was obtained and surgical biopsy of the subconjunctival lesion was performed; histopathology confirmed the diagnosis of plasmacytoma. RESULTS: Subconjunctival biopsy revealed a plasma cell neoplasm infiltrate in the episcleral layer...
November 16, 2016: Cornea
https://www.readbyqxmd.com/read/27848179/human-mutt-homologue-1-mrna-overexpression-correlates-to-poor-response-of-multiple-myeloma
#7
Huixing Zhou, Yuan Jian, Yun Leng, Nian Liu, Ying Tian, Guorong Wang, Wen Gao, Guangzhong Yang, Wenming Chen
Human MutT homologue 1 (MTH1) is a human 8-oxo-dGTPase that eradicates oxidized bases in the nucleotide pool and DNA. MTH1 is critical for RAS-transformed cancer cell survival, whereas it is dispensable in normal cells and tissues. Here, we determined the expression of MTH1 in multiple myeloma (MM) cell lines and MM patients' CD138 (+) cells and analyzed its potential clinical significance. We detected overexpression of MTH1 mRNA in three cell lines (RPMI 8226, U266, and H929). MTH1 mRNA expression of RPMI8226 was higher than that of U266 and H929...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27784369/-correlation-between-expression-of-cd200-and-regulatory-t-cells-in-multiple-myeloma-and-its-significance-in-prognostic-stratification
#8
Ming-Xia Zhu, Wen-Li Wan, Hai-Shen Li, Yan-Fang Wang, Jing Wang, Hui-Sen Ling, Xin-Xing Yan, Xiao-Yan Ke
OBJECTIVE: To study the correlation between expression of CD200 and regulatory T cells (Tregs) in multiple myeloma(MM) patients and to explore its significance in prognostic stratification. METHODS: CD200 and other immunophenotypes, including CD38, CD138, CD56, CD19, CD20, CD117, cytoplasm light chain Kappa and Lambda in bone marrow samples, and Tregs in peripheral blood were detected by flow cytometry from 78 newly diagnosed MM patients. Serum concentrations of hemoglobin(Hb), β2 microglobulin (β2-MG) and lactate dehydrogenase (LDH) were detected, respectively...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27683032/the-role-of-sh3gl3-in-myeloma-cell-migration-invasion-stemness-and-chemo-resistance
#9
Ruoying Chen, Hong Zhao, Dan Wu, Chen Zhao, Weiling Zhao, Xiaobo Zhou
Multiple myeloma (MM) is an incurable cancer characterized by clonal expansion of malignant plasma cells in the bone marrow and their egress into peripheral blood. The mechanisms of myeloma cells migration/invasion have remained unclear. Herein, we found SH3GL3 was highly expressed in the CD138-negative (CD138-) myeloma cells. The migration/invasion capability of CD138- cells was significantly higher than that in the CD138-positive (CD138+) cells. Silencing SH3GL3 using shRNA reduced myeloma cells migration/invasion...
September 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27677741/pharmacogenomics-and-chemical-library-screens-reveal-a-novel-scf-skp2-inhibitor-that-overcomes-bortezomib-resistance-in-multiple-myeloma
#10
E Malek, M A Y Abdel-Malek, S Jagannathan, N Vad, R Karns, A G Jegga, A Broyl, M van Duin, P Sonneveld, F Cottini, K C Anderson, J J Driscoll
While clinical benefit of the proteasome inhibitor (PI) bortezomib for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin (Ub) ligase Skp1-Cullin-1-Skp2 (SCF(Skp2)) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCF(Skp2) activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B...
September 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27634757/cell-adhesion-molecule-cd166-drives-malignant-progression-and-osteolytic-disease-in-multiple-myeloma
#11
Linlin Xu, Khalid S Mohammad, Hao Wu, Colin Crean, Bradley Poteat, Yinghua Cheng, Angelo A Cardoso, Christophe Machal, Helmut Hanenberg, Rafat Abonour, Melissa A Kacena, John Chirgwin, Attaya Suvannasankha, Edward F Srour
Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166(+) multiple myeloma cells homed more efficiently than CD166(-) cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27634301/identification-of-doxorubicin-as-an-inhibitor-of-the-ire1%C3%AE-xbp1-axis-of-the-unfolded-protein-response
#12
Dadi Jiang, Connor Lynch, Bruno C Medeiros, Michaela Liedtke, Rakesh Bam, Arvin B Tam, Zhifen Yang, Muthuraman Alagappan, Parveen Abidi, Quynh-Thu Le, Amato J Giaccia, Nicholas C Denko, Maho Niwa, Albert C Koong
Activation of the IRE1α-XBP1 branch of the unfolded protein response (UPR) has been implicated in multiple types of human cancers, including multiple myeloma (MM). Through an in silico drug discovery approach based on protein-compound virtual docking, we identified the anthracycline antibiotic doxorubicin as an in vitro and in vivo inhibitor of XBP1 activation, a previously unknown activity for this widely utilized cancer chemotherapeutic drug. Through a series of mechanistic and phenotypic studies, we showed that this novel activity of doxorubicin was not due to inhibition of topoisomerase II (Topo II)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27582537/evaluation-of-in-vitro-effects-of-various-targeted-drugs-on-plasma-cells-and-putative-neoplastic-stem-cells-in-patients-with-multiple-myeloma
#13
Katharina Blatt, Harald Herrmann, Gabriele Stefanzl, Wolfgang R Sperr, Peter Valent
Multiple myeloma (MM) is a malignancy characterized by monoclonal paraproteinemia and tissue plasmocytosis. In advanced MM cytopenia and osteopathy may occur. Although several effective treatment strategies have been developed in recent years, there is still a need to identify new drug targets and to develop more effective therapies for patients with advanced MM. We examined the effects of 15 targeted drugs on growth and survival of primary MM cells and 5 MM cell lines (MM.1S, NCI-H929, OPM-2, RPMI-8226, U-266)...
August 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27557643/treatment-of-acquired-drug-resistance-in-multiple-myeloma-by-combination-therapy-with-xpo1-and-topoisomerase-ii-inhibitors
#14
Joel G Turner, Jana L Dawson, Steven Grant, Kenneth H Shain, William S Dalton, Yun Dai, Mark Meads, Rachid Baz, Michael Kauffman, Sharon Shacham, Daniel M Sullivan
BACKGROUND: Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease. METHODS: We investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients...
August 24, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27533084/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#15
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27495052/monotypic-plasma-cell-interstitial-nephritis-as-the-only-clinical-manifestation-in-a-patient-with-previously-undiagnosed-indolent-multiple-myeloma-a-case-report
#16
Philippe Attias, Anissa Moktefi, Marie Matignon, Jehan Dupuis, Céline Debiais-Delpech, Philippe Grimbert, Philippe Lang, Vincent Audard
INTRODUCTION: Predominantly monotypic plasma cell infiltrates are an uncommon renal finding in patients with malignant lymphoplasmacytic proliferation. CASE PRESENTATION: We report the case of a 52-year-old man with chronic kidney disease and significant proteinuria associated with a monoclonal immunoglobulin spike (IgGκ). Kidney biopsy revealed the presence of atypical multinucleated CD138 plasma cells with voluminous nuclei stained exclusively with a κ antibody...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27408376/flow-cytometry-in-diagnosis-of-myelomatous-pleural-effusion-a-case-report
#17
Parul Arora, Sanjeev Kumar Gupta, Nabhajit Mallik, Reena Mittal, Om Dutt Sharma, Lalit Kumar
Plasma cell myeloma is a multifocal plasma cell neoplasm associated with increased monoclonal protein in serum and/or urine. Pleural effusions in patients with myeloma are uncommon (6 %). However, effusions due to direct infiltration of the pleura by plasma cells (myelomatous pleural effusion) are extremely rare (<1 %) and usually seen with IgA myeloma. The diagnosis of such cases requires pleural fluid cytology, electrophoresis or pleural biopsy. We present a case of myelomatous pleural effusion diagnosed using flow cytometry immunophenotyping in addition to the pleural fluid cytology...
June 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27396960/concurrent-myelomatous-pleural-effusion-and-extramedullary-mediastinal-involvement-as-an-initial-manifestation-of-multiple-myeloma
#18
George Williams, Dipen Kadaria, Amik Sodhi
BACKGROUND Myelomatous pleural effusion (MPE) is a rare occurrence in patients with multiple myeloma (MM). Fewer than 20 cases of MPE have been reported as an initial manifestation of MM. Extramedullary plasmacytoma (EMP) occurs in fewer than 5% patients with MM, and mediastinal EMP is even rarer, with only about 80 cases reported in the literature. We present a case study involving a patient with concurrent MPE and mediastinal EMP as an initial manifestation of MM. CASE REPORT The patient was a 74-year-old nonsmoking female with a 3-month history of exertional dyspnea and back pain...
2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27364558/syndecan-1-cd138-suppresses-apoptosis-in-multiple-myeloma-by-activating-igf1-receptor-prevention-by-synstatinigf1r-inhibits-tumor-growth
#19
DeannaLee M Beauvais, Oisun Jung, Yang Yang, Ralph D Sanderson, Alan C Rapraeger
Syndecan-1 (Sdc1/CD138) expression is linked to disease severity in multiple myeloma, although the causal basis for this link remains unclear. Here we report that capture of the IGF1 receptor (IGF1R) by Sdc1 suppresses ASK1-dependent apoptosis in multiple myeloma cells. Sdc1 binds two different fractions of IGF1R, one that is constitutively active and a second that is activated by IGF1 ligand. Notably, IGF1R kinase activity in both fractions is blocked by synstatinIGF1R (SSTNIGF1R), a peptide that inhibits IGF1R capture by Sdc1, as well as by a truncated peptide (SSTNIGF1R-T) that appears to be specific for multiple myeloma cells...
September 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27364300/a-case-of-lethal-idiopathic-plasmacytic-lymphadenopathy-with-polyclonal-hypergammaglobulinemia-a-medical-challenge-for-the-forensic-pathologist
#20
Lucia Tattoli, Biagio Solarino, Oronzo Schiraldi, Giancarlo Di Vella
A rare case of lethal idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia with chronic renal failure is described. A 40-year-old woman who had suffered from upper airways disease was admitted to the Emergency Room with acute renal failure and hypergammaglobulinemia. She developed pericardial effusion, a pruritic rash, splenomegaly and fell into a coma after 6 days. Multiple myeloma, infection, collagenopathy, and coagulopathy were ruled out. Finally, a form of malignant hypergammapathy was suspected...
July 2016: Journal of Forensic Sciences
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